Supplements, micronutrients, anti-inflammatory eating, gut health, and the dietary patterns that actually move clinical biomarkers — written without the wellness industry bias.
Core supplement evidence grades
Clinical Reference
Evidence grades based on human RCT quality, effect size consistency, and clinical relevance. This is a living reference — updated as new data emerges.
| Supplement | Optimal Dose | Timing | Grade | Clinical Note |
|---|---|---|---|---|
| Omega-3 (EPA+DHA) | 2–4g combined EPA+DHA | With meals | A | Triglyceride reduction, anti-inflammatory, cognitive support. Test AA:EPA ratio to guide dosing. |
| Vitamin D3 | 2,000–5,000 IU/day | With fat-containing meal | A | Always pair with K2 (MK-7 100–200mcg). Target serum 25(OH)D: 40–60 ng/mL. Test before dosing. |
| Magnesium Glycinate | 200–400mg elemental Mg | Evening preferred | A | Glycinate for sleep/anxiety; threonate for cognition; malate for energy/muscle. Oxide is poorly absorbed. |
| Creatine Monohydrate | 3–5g/day | Post-workout or anytime | A | Strongest safety and efficacy record of any supplement. Cognitive and muscle benefits in older adults. |
| Zinc (with Copper) | 15–30mg Zn, 1–2mg Cu | Away from iron | B | Always pair copper when supplementing zinc long-term. Deficiency common with poor diet, GI conditions. |
| Berberine | 500mg 2–3× daily | Before meals | B | AMPK activator; comparable to metformin in some glucose studies. Drug interactions — check before prescribing. |
| Vitamin K2 (MK-7) | 100–200mcg/day | With D3 and fat | B | Directs calcium to bones rather than arteries. Critical when supplementing D3 above 2,000 IU. |
| Ashwagandha (KSM-66) | 300–600mg/day | Morning or evening | C | Cortisol reduction and stress response improvement shown in several RCTs. Thyroid interaction possible. |
| CoQ10 (Ubiquinol) | 100–300mg/day | With fat-containing meal | C | Ubiquinol form preferred over ubiquinone. Indicated if on statin therapy; otherwise evidence mixed. |
| Probiotics | Strain-specific dosing | Before meals | C | Efficacy is strain-specific. Lactobacillus rhamnosus GG and Saccharomyces boulardii have best evidence. |
| Collagen Peptides | 10–15g/day | With Vitamin C | C | Type I/III for skin and connective tissue; Type II for joints. Add Vitamin C to support synthesis. |
| Iron (therapeutic) | Ferrous bisglycinate preferred | Alternate day dosing | D — Rx Only | Do not supplement without documented deficiency. Test ferritin, TIBC, transferrin saturation first. |
Vitamin D3 without K2 can drive calcium into arteries rather than bones. The MK-7 form of K2 has a half-life of 72 hours versus 6 hours for MK-4. Dosing, ratios, testing targets, and the clinical logic behind the combination.
EPA drives anti-inflammatory prostaglandin production; DHA supports neuronal membrane fluidity. The optimal EPA:DHA ratio differs by clinical indication — CVD, depression, and triglycerides each have different targets.
Krill oil delivers omega-3s in phospholipid form with superior absorption. Algae oil is the only plant-based EPA+DHA source — and it's what fish eat in the first place. A clinical breakdown of the forms that matter.
The ideal omega-6 to omega-3 ratio is approximately 4:1. The average American diet sits at 15–20:1, driven by seed oils and processed food. What this means for systemic inflammation, cardiovascular risk, and metabolic disease.
Lab reference ranges (20–50 ng/mL) reflect deficiency prevention, not optimal health. Most longevity-focused clinicians target 40–60 ng/mL. How to test, interpret, and dose to target without toxicity.
Magnesium oxide is 4% bioavailable. Glycinate reaches 80%+. Threonate uniquely crosses the blood-brain barrier and raises CSF magnesium. A form-by-form clinical guide for sleep, cognition, muscle, and cardiovascular support.
Zinc and copper share the same intestinal transporter — supplementing one chronically depletes the other. Signs of deficiency, the serum zinc testing caveat, and the clinical importance of the copper-zinc ratio.
95% of serotonin is produced in the gut. The vagus nerve carries bidirectional signals between the enteric and central nervous systems. The clinical implications for anxiety, depression, and neuroinflammation are substantial.
Probiotics are living organisms; prebiotics are their food; postbiotics are their metabolic byproducts — including short-chain fatty acids like butyrate. The clinical distinction matters for IBS, IBD, and microbiome restoration.
Intestinal hyperpermeability is real and measurable — via lactulose/mannitol ratio or zonulin testing. It's implicated in autoimmunity and metabolic disease. But the supplement industry's version bears little resemblance to the science.
hs-CRP, IL-6, TNF-α, and homocysteine are the inflammatory markers that predict chronic disease decades before symptoms appear. Dietary patterns — Mediterranean, whole food, polyphenol-rich — consistently move these markers.
Curcumin's bioavailability is notoriously poor — piperine or phospholipid complexes improve it 20-fold. Quercetin shows consistent anti-inflammatory and senolytic activity in human trials. The evidence, form by form.
Standard CRP detects acute inflammation (threshold 10 mg/L). hs-CRP detects chronic low-grade inflammation (threshold 0.5 mg/L). Anything above 2.0 mg/L is associated with significantly elevated cardiovascular risk.
The 0.8g/kg RDA was set to prevent deficiency, not to optimize health. Meta-analyses consistently support 1.6–2.2g/kg/day for adults pursuing muscle preservation — especially over 50. Timing, distribution, and leucine thresholds explained.
Adults lose 3–8% of muscle mass per decade after 30, accelerating after 60. DEXA-measured appendicular lean mass index predicts metabolic disease, falls, hospitalization, and all-cause mortality better than BMI in older adults.
GI measures glucose response per 100g of carbohydrate. GL accounts for serving size. Insulin index includes non-carbohydrate insulin triggers like dairy and refined proteins. For insulin-resistant patients, the insulin index is the most clinically relevant metric.
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